Current research in this project has focused on the actions of gonadotropins and GnRH agonists upon the maturing ovarian granulosa cell. We have previously shown that FSH induces granulosa-cell maturation via an increase in cyclic AMP production, and that the inhibitory effects of GnRH agonists (GnRHa) are associated with impairment of adenylate cyclase activity and decreased cyclic AMP formation. Such effects of GnRHa were shown to be mediated by specific GnRH receptors in the granulosa cell that are coupled to a calcium-dependent mechanism, as in the pituitary gland. However, in contrast to their stimulatory effects on gonadotropin release, GnRH agonists exert predominately inhibitory actions at the ovarian level. These actions were shown to include marked suppression of receptors for FSH as well as for LH and prolactin, with a consequent decrease in FSH-stimulated adenylate cyclase activity. The stimulatory actions of GnRHa on ovarian function become more prominent with increasing maturation of the granulosa cell, and include increases in ovarian weight, basal adenylate cyclase activity and prolactin receptors, and luteinization of mature ovarian follicles. In addition to its effects on granulosa-cell maturation and expression of receptors for LH and prolactin, FSH also promotes the formation of its own receptors and this action has now been shown to be mediated by cyclic AMP, and to be prevented by GnRHa. Also, the expression of gonadotropin receptors by FSH and other cAMP-inducing ligands has been shown to be markedly enhanced by estrogens, indicating the importance of synergistic interactions between FSH and estrogen in the maturation of granulosa cell function. The mechanism of receptor induction by FSH will be further explored by analysis of mRNA and receptor protein synthesis in the cultured granulosa cell system. It is expected that this system will provide a valuable model for studies on the combined actions of steroid and gonadotropic hormones during granulosa cell maturation, and for the investigation of gonadotropin receptor synthesis and turnover during defined in vitro conditions.